Leonid B. Volodarsky

Synthetic chemistry of stable nitroxides

Introduction to Nitroxide Chemistry. Generation and Chemical Properties of the Nitroxyl Group. Synthetic Chemistry of Stable Nitroxides. Complexes with Metal-Nitroxyl Group Coordination. New Approaches to Generation of Heterocyclic Nitroxides Using Organometal Reagents. References. Index.

COMPLEXES OF CHLORINE DIOXIDE WITH NITROXYL RADICALS

Abstract Chlorine dioxide forms red-colored ( λ max =480 nm) CT complexes with persistent piperidine and imidazoline nitroxyl radicals in diethyl ether, n -pentane, carbon tetrachloride, methylene chloride and on silica gel surface. Equilibrium constants, enthalpy and entropy of formation and extinction coefficient of the complex between ClO 2 and 2.2,6,6-tetramethyl-4-oxypiperidin-1-oxyl 1 in diethyl ether were determined. In Et 2 O the complex is stable under normal conditions, in other media it transforms into the oxoammonium salt.

Dipole-Stabilized Carbanions in Series of Cyclic Aldonitrones. Part 2: Reactions of the Metalated Aldonitrones—Derivatives of 3-Imidazoline 3-Oxide and 2H-Imidazole 1-Oxide with Aldehydes and Ketones

Abstract Metalated aldonitrones of 3-imidazoline 3-oxide and 2H-imidazole 1-oxide series react with a wide variety of aldehydes and ketones leading to the unknown α-hydroxymethyl nitrones. Reaction of 2,2-dimethyl-4-phenyl-2H-imidazole 1-oxide with allylacetone spontaneously lead to tricyclic 3,3,8-trimethyl-1-phenyl-5a,6,7,8-tetrahydro-3H,5H-4-oxa-2,3a-diaza-cyclopenta[c]pentalen-8-ol. The hydroxy group of (1,2,2,5,5-pentamethyl-2,5-dihydro-1H-imidazol-3-oxide-4-yl)phenylmethanol is substituted with piperidine to give, after further transformations, (1,2,2,5,5-pentamethyl-2,5-dihydro-1H-imidazol-4-yl)phenylmethanone.

Stable nitroxides with hydrogen at α-carbon of the nitroxyl group

Abstract The reactions of 1-hydroxy-3-imidazoline-3-oxides containing hydrogen in the 2-position with PhLi or PhMgBr lead to acyclic α-hydroxylaminooximes. The oxidation of the latter gives stable acyclic nitroxides with hydrogen at the α-carbon atom.

Interaction of heterocyclic nitrones with organometallic reagents as a method for the synthesis of new types of nitroxides

Abstract The reactions of heterocyclic nitroxides: 3-imidazoline-3-oxides, 2H- (4H)-imidazole mono- and dioxides, dihydropyrazine-1,4-dioxides, with organometallic reagents and subsequent oxidation led to heterocyclic nitroxides of 3-(2)-imidazoline and 3-(2)-imidazoline-3-oxide, dihydropyrazine oxide, monocyclic imidazolidine biradicals and stable acyclic nitroxides with hydrogen at the α-carbon atom.

Synthesis and some properties of heterocyclic amidine derivatives of 3-imidazoline nitroxides

Abstract The interaction of 2,2,5,5-tetramethyl-3-imidazoline-3-oxide-1-oxyl with isocyanates leads to oxadiazolidine cycloadducts which are smoothly transformed into amidines - 4-R-amino-2,2,5,5-tetramethyl-3-imidazoline-1-oxyles when treated with nucleophilic reagents. This reaction was applied to the synthesis of some paramagnetic amidines containing various functional groups which may be used as spin labels having a pH-sensitive ESR spectrum. The mechanism of transformation of oxadiazolidines into amidines and the tautomeric equilibrium of the amidines synthesized are discussed.

Unexpected transformation of 1,2-bis(N-methoxy-N-nitrosoamino)cycloalkanes: First synthesis of 4,5-dihydro-1,2,3-triazole 2-oxides

Abstract Thermolysis of 1,2-bis( N -methoxy- N -nitrosoamino)cycloalkanes in organic solvents led to 4,5-dihydro-1,2,3-triazole 2-oxides.

Synthesis and Inhibitory Effect on Platelet Aggregation and Antihypertensive Activity of 1‐Hydroxy‐2,5‐dihydro‐1H‐imidazole‐2‐ carboxylic Acid 3‐Oxides, 1,3‐Dihydroxyimidazolidine‐2‐carboxylic Acids, and 1,4‐Dihydroxy‐2,3‐piperazinediones

The reaction of 1,2‐hydroxylamino‐oximes 1 with pyruvic or glyoxylic acid and of 1,2‐bishydroxylamines 4 with glyoxylic acid resulted in 2,5‐dihydro‐1H‐imidazole‐2‐carboxylic acid 3‐oxides 2 and 2‐imidazolidinecarboxylic acids 5, respectively. It was found that hydroxylamino acids 2 and 1,4‐dihydroxy‐2,3‐piperazinediones 7 showed marked inhibitory effect on platelet aggregation. 1‐Hydroxy‐2‐methyl‐1,5,6,7,8,8a‐hexahydro‐2H,4H‐cycloheptimidazole‐2‐carboxylic acid 3‐oxide 2e exhibited antihypertensive activity.

New 3-Imidazoline Derivatives and their Palladium(II) Complexes

The protection of the hydroxy group of 1-hydroxy-2.2.4.5.5-pentamethyl-3-imidazoline by a t-butyldimethylsilyl group gives the silane 1 which allows via the 4-lithium salt the preparation of 4-substituted derivatives, i. e. a dithiocarboxylic acid (2), a disulfide (3), a phosphane (4) and a thioether (5). Oxidation of 4-lithiated 1 yields under C–C coupling an ethylene bridged bis(3-imidazoline) (6). From these compounds Pd(II) and Pt(II) complexes M(4)2Cl2 (M = Pd, Pt and Pd(5)Cl2 were prepared and the structure of the dithiocarboxylate chelate complex Pd(2-H+)2 (7) was determined by X-ray diffraction. Cleavage of the silyl group from 7 gives complex 8 which can be oxidized to the corresponding diradical (9). Complex 9 was characterized by its EPR spectrum. Measurements of the magnetic susceptibility of 9 reveal strong antiferromagnetic coupling between the two spins at low temperatures. Neue 3-Imidazolin-Derivate und ihre Palladium(II)-Komplexe In 1-Hydroxy-2,2,4,5,5-pentamethyl-3-imidazolin last sich die Hydroxygruppe durch t-Butyldimethylsilyl schutzen und aus diesem Silan 1 sind uber das 4-Lithium-Salz verschiedene 4-substituierte Imidazolin-Derivate zuganglich: eine Dithiocarbonsaure (2), ein Disulfid (3), ein Phosphan (4) und ein Thioether (5). Die Oxidation des lithierten 1 ergibt unter C–C-Kupplung ein Ethylen-verbrucktes Bis(3-imidazol). Mit den Liganden wurden die Pd(II)- und Pt(II)-Komplexe M(4)2Cl2 (M = Pd, Pt) und Pd(5)Cl2 erhalten. Die Struktur des Dithiocarboxylat-Komplexes Pd(2-H+)2 (7) wurde rontgenographisch bestimmt. Der durch Abspaltung der Silylgruppe aus 7 erhaltene Komplex 8 kann zum Dinitroxid-diradikal 9 oxidiert werden. Komplex 9 wurde durch sein EPR-Spektrum charakterisiert. Magnetische Messungen zeigen fur 9 bei tiefen Temperaturen starke antiferromagnetische Wechselwirkungen.

Synthesis of acetonine nitroxide radical and 1-hydroxy-2,2,4,6,6-pentamethyl-1,2,5,6-tetrahydropyrimidine

Abstract An oxidation of acetonine with hydrogen peroxide 30% in strong basic water media in the presence of sodium tungstate with subsequent reduction of reaction product with hydrazine hydrate afforded up to 50% yields of the title hydroxyderivative. Mild oxidation of this compound with MnO2 in ether gave acetonine nitroxide radical quantitatively.